Venlafaxine, (±)-1-[2-(Dimethylamino)-1-(4-ethyoxyphenyl)ethyl]cyclo-hexanol is the first of a class of anti-depressants. Venlafaxine acts by inhibiting re-uptake of norepinephrine and serotonin, and is an alternative to the tricyclic anti-depressants and selective re-uptake inhibitors. Venlafaxine has the following chemical formula, Formula I:

O-desmethylvenlafaxine, 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol, is a major metabolite of venlafaxine and has been reported to inhibit norepinephrine and serotonin uptake. See Klamerus, K. J. et al., “Introduction of the Composite Parameter to the Pharmacokinetics of Venlafaxine and its Active O-Desmethyl Metabolite,” J. Clin. Pharmacol. 32:716-724 (1992). O-desmethylvenlafaxine has the following chemical formula, Formula II:

Processes for the synthesis of O-desmethylvenlafaxine, comprising a step of demethylation of the phenol group of venlafaxine, are described in U.S. Pat. Nos. 7,026,508 and 6,689,912, and in U.S. publication No. 2005/0197392, which are incorporated herein by reference.
The synthesis disclosed in the above references is performed according to the following scheme:
“MBC” refers to methyl benzyl cyanide, “CMBC” refers to cyclohexyl methylbenzyl cyanide, “DDMV” refers to didesmethyl venlafaxine, and “ODV” refers to O-desmethylvenlafaxine.
However, the processes disclosed in the above US patents and US patent applications all remain problematic when applied to industrial scale production. The process in U.S. Pat. No. 7,026,508 uses L-selectride, a compound which is very problematic when scaling up the process for industrial application. Further, the process disclosed in US Application Publication No. 2005/0197392 uses lithiumdiphenyl phosphine, a compound which handling and use in industrial scale processes is extremely dangerous. Also, the process disclosed in U.S. Pat. No. 6,689,912 uses methanol as a solvent, which use is problematic when traces of methanol remain and in subsequent process steps when high temperatures are applied.
Therefore, there is a need in the art for a new synthetic route for obtaining O-desmethylvenlafaxine, using a precursor of venlafaxine to directly obtain O-desmethylvenlafaxine.